Contribution of ionic silver to genotoxic potential of nanosilver in human liver HepG2 and colon Caco2 cells evaluated by the cytokinesis‐block micronucleus assay

Abstract

Extensive human exposure to food-and cosmetics-related consumer products containing nanosilver is of public concern because of the lack of information about their safety. Genotoxicity is an important endpoint for the safety and health hazard assessment of regulated products including nanomaterials. The in vitro cytokinesis-block micronucleus (CBMN) assay is a very useful test for predictive genotoxicity testing. Recently, we have reported the genotoxicity of 20 nm nanosilver in human liver HepG2 and colon Caco2 cells evaluated using the CBMN assay. The objective of our present study was three-fold: (i) to evaluate if HepG2 and Caco2 cells are valuable in vitro models for rapid genotoxicity screening of nanosilver; (ii) to test the hypothesis that the nanoparticle size and cell types are critical determinants of its genotoxicity; and (iii) to determine if ionic silver contributes to the nanosilver genotoxicity. With these objectives in mind, we evaluated the genotoxic potential of 50 nm nanosilver of the same shape, composition, surface charge, obtained from the same commercial source, under the same experimental conditions and the same genotoxic CBMN endpoint used for the previously tested 20 nm silver. The ionic silver (silver acetate) was also evaluated under the same conditions. Results of our study show that up to the concentrations tested in these cell types, the smaller (20 nm) nanosilver induces micronucleus formation in both the cell types but the larger (50 nm) nanosilver and the ionic silver provide a much weaker response compared with controls under the same conditions. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Genotoxic effects of silver nanoparticles with/without coating in human liver HepG2 cells and in mice

“…The comet assay and the cytokinesis‐block micronucleus assay showed that both AgNPs and PVP‐AgNPs could induce DNA and chromosome damage in HepG2 cells. Additionally, Sahu et al found that in HepG2 cells and Caco cells, the frequency of micronucleus binuclear cells induced by nanosilver at the concentration range of 0.5‐15 μg/mL increased in a concentration‐ and time‐dependent manner (Sahu, Roy, Zheng, & Ihrie, ). Papageorgiou et al () confirmed that the mitotic index of MCF‐7 cells and HepG2 cells decreased with the increase of nanosilver concentration, they also observed different types of chromosome aberrations.…”

Genotoxicity of Silver Nanoparticles

“…OECD TG 487 [64] was followed in studies carried out by five authors: Sahu et al [73], Ivask et al [74], Guo et al [72], Sahu et al [75] and Sahu et al [76]. According to OECD TG 487 [64], human peripheral blood lymphocytes and some rodent cell lines such as CHO, V79 and L5178Y or human cell lines such as TK6 are considered suitable for performing this assay; however, other cell lines such as HT29, Caco-2, HepG2 and A549, which have been used in several studies, have not been extensively validated by OECD TG 487 [64].…”

Biological Activity of Silver Nanoparticles and Their Applications in Anticancer Therapy

“…Tests on different human cell line models showed tissue-dependent sensitivity and the importance for applied doses potentially used in anticancer therapies of NPs. The same research group, working again with HepG2 and Caco-2 cells, discussed the genotoxic potential of AgNPs as a result of chromosome damage during mitosis, where chromosomal abnormalities occurred as seen by micronucleus formation (Mn assay) [43]. The nanosilver genotoxicity resulted in viability reduction in a dosedependent manner and was explained by cytokinesis blockade [43], which could be a result of abnormal formation of histone H2A, that disrupts cellular division and proper chromatin (chromosome) formation [44].…”